However, in most cases, there are no adverse immunological reactions in the female reproductive tract to ejaculated spermatozoa. 7 The reason for this could be the immuno-protective effect of seminal plasma, 8,9 which gets mixed with spermatozoa during ejaculation. In addition, factors like immune insult from bacterial infections 10,11 and female sex hormones 12 have been shown to influence the viability of spermatozoa and immune response against them in females. It has been found that there is sequential developmental change in the immunogenicity of a spermatozoon as it moves from rete testis toward the caput epididymidis, corpus epididymidis, and finally the cauda epididymidis. Indeed, it has been shown that rete testis spermatozoa are most immunogenic and cauda epididymidis spermatozoa are the least. This suggests that the spermatozoon loses its immunogenicity as it moves from rete testis toward the cauda epididymidis, and the immunogenicity of ejaculated spermatozoa could be less than those from the cauda epididymidis. ABSTRACT: Immunobiological changes in spermatozoa within the male reproductive tract are vital for their viability, and hence for reproductive efficiency. The secretions of the seminal vesicles have immunosuppressive property that attenuates the antigenic effects of spermatozoa in the male reproductive tract. However, when spermatozoa find a way to outside of the rete testis or epididymis due to trauma or infection, they can cause significant inflammatory and immunological reactions in the surrounding tissues. This has also been observed in the female reproductive tract. However, such cases are rare and the reason for this is unknown. Antisperm antibodies are the main cause of infertility in humans. The purpose of this review is to analyze these immunobiological changes from the time of spermatozoa formation in rete testis to their role in fertilizing the oocytes in the female reproductive tract.